Early life stress affects cerebral glucose metabolism in adult rhesus monkeys (Macaca mulatta)

Abstract

Early life stress (ELS) is a risk factor for anxiety, mood disorders and alterations in stress responses. Less is known about the long-term neurobiological impact of ELS. We used [18F]-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) to assess neural responses to a moderate stress test in adult monkeys that experienced ELS as infants. Both groups of monkeys showed hypothalamic-pituitary-adrenal (HPA) axis stress-induced activations and cardiac arousal in response to the stressor. A whole brain analysis detected significantly greater regional cerebral glucose metabolism (rCGM) in superior temporal sulcus, putamen, thalamus, and inferotemporal cortex of ELS animals compared to controls. Region of interest (ROI) analyses performed in areas identified as vulnerable to ELS showed greater activity in the orbitofrontal cortex of ELS compared to control monkeys, but greater hippocampal activity in the control compared to ELS monkeys. Together, these results suggest hyperactivity in emotional and sensory processing regions of adult monkeys with ELS, and greater activity in stress-regulatory areas in the controls. Despite these neural responses, no group differences were detected in neuroendocrine, autonomic or behavioral responses, except for a trend towards increased stillness in the ELS monkeys. Together, these data suggest hypervigilance in the ELS monkeys in the absence of immediate danger.

Fetal Glucocorticoid Exposure Is Associated with Preadolescent Brain Development

“…Interestingly, our observation is similar to a recent non-human primate study assessing the consequences of postnatal stress exposure in which group differences in brain development were observed despite the absence of group differences in behavior (104). Cortical thickness may be a more sensitive measure than behavioral observations and may detect prodromal risk for behavioral dysfunction at later ages.…”

A Preliminary Study of the Infl uence of Age of Onset and Childhood Trauma on Cortical Thickness in Major Depressive Disorder

“…Chronic stress increases the state of alertness [59], which is associated with the thalamus [58]. Consistent with our result, a Positron Emission Tomography study [60] revealed significantly greater regional cerebral glucose metabolism in thalamus in adult monkeys who experienced early life stress compared to controls, and another study [61] showed that young adults who experienced corporal punishment in childhood exhibited increased cerebral blood volume in the thalamus. Greater activation or increased volumes in the thalamus might suggest a general problem with sensory information processing, perhaps indicating hyper-vigilance, which is thought to be involved in the pathophysiology of GAD.…”

Early-life social adversity and developmental processes in nonhuman primates

“…These affective responses, also characterized by pronounced behavioral inhibition, in SOR-exposed macaques persist well into adulthood [4]. Some behavioral effects of ELSA may not be long lasting, as macaques that experienced STS as infants displayed normative behavioral reactivity when placed in short-term social isolation as adults [5]. ELSA alters distress behavior and vocalizations in both macaques and marmosets.…”

“…Adults that experienced STS as infants showed an increase in glucose uptake in the orbitofrontal cortex (OFC) and superior temporal sulci, regions that are critical for decision-making, emotional regulation, and social behavior. STS was also associated with reduced glucose uptake in the hippocampus, a region associated with inhibitory control over the stress response [5]. …”